Antagonists of phosphatidylinositol 3-kinase block activation of several novel protein kinases in neutrophils - PubMed (original) (raw)
Comparative Study
. 1995 May 12;270(19):11684-91.
doi: 10.1074/jbc.270.19.11684.
Affiliations
- PMID: 7744808
- DOI: 10.1074/jbc.270.19.11684
Free article
Comparative Study
Antagonists of phosphatidylinositol 3-kinase block activation of several novel protein kinases in neutrophils
J Ding et al. J Biol Chem. 1995.
Free article
Abstract
Several novel protein kinases are known to be rapidly activated in neutrophils stimulated with the chemoattractant fMet-Leu-Phe (fMLP). These kinases include a histone H4 protein kinase and several renaturable kinases with molecular masses of about 69, 63, 49, and 40 kDa. The renaturable kinases can catalyze the phosphorylation of a peptide that corresponds to residues 297-331 of the 47-kDa subunit of the NADPH-oxidase system (p47-phox). Previous studies have indicated that the activation of all of these protein kinases involves an uncharacterized stimulatory pathway and/or novel second messenger. The studies reported herein were undertaken to determine if phosphatidylinositol 3-kinase (PI3-K) is a component of this pathway. We report that certain chromosome derivatives (e.g. 2-(4-morpholinyl)-8-phenylchromone (LY294002)) and wortmannin, which inhibit PI3-K by distinct mechanisms, blocked activation of all of these novel kinases. These antagonists also inhibited the phosphorylation of p47-phox (about 50%) and O2.- release (about 80%) in cells stimulated with fMLP, but not with 4 beta-phorbol 12-myristate 13-acetate. A strong correlation exists between the amounts of these antagonists required to produce 50% inhibition of PI3-K in vitro and O2.- release in vivo. In contrast, a single atom substitution of LY294002 produced a compound (LY303511) that did not inhibit PI3-K. Compound LY303511 did not appreciably inhibit the activation of the novel protein kinases or O2.- generation. These data strongly suggest that PI3-K is involved in the activation of several novel protein kinases in neutrophils, one or more of which may be involved in O2.- release.
Similar articles
- Inhibition of neutrophil oxidative burst and granule secretion by wortmannin: potential role of MAP kinase and renaturable kinases.
Sue-A-Quan AK, Fialkow L, Vlahos CJ, Schelm JA, Grinstein S, Butler J, Downey GP. Sue-A-Quan AK, et al. J Cell Physiol. 1997 Jul;172(1):94-108. doi: 10.1002/(SICI)1097-4652(199707)172:1<94::AID-JCP11>3.0.CO;2-O. J Cell Physiol. 1997. PMID: 9207930 - Investigation of neutrophil signal transduction using a specific inhibitor of phosphatidylinositol 3-kinase.
Vlahos CJ, Matter WF, Brown RF, Traynor-Kaplan AE, Heyworth PG, Prossnitz ER, Ye RD, Marder P, Schelm JA, Rothfuss KJ, et al. Vlahos CJ, et al. J Immunol. 1995 Mar 1;154(5):2413-22. J Immunol. 1995. PMID: 7868907 - Protein kinase C and the activation of the human neutrophil NADPH-oxidase.
Tauber AI. Tauber AI. Blood. 1987 Mar;69(3):711-20. Blood. 1987. PMID: 3545319 Review. No abstract available. - Chemoattractant signaling and leukocyte activation.
Bokoch GM. Bokoch GM. Blood. 1995 Sep 1;86(5):1649-60. Blood. 1995. PMID: 7654998 Review. No abstract available.
Cited by
- The present and future of PI3K inhibitors for cancer therapy.
Castel P, Toska E, Engelman JA, Scaltriti M. Castel P, et al. Nat Cancer. 2021 Jun;2(6):587-597. doi: 10.1038/s43018-021-00218-4. Epub 2021 Jun 17. Nat Cancer. 2021. PMID: 35118422 Free PMC article. - Shear and Integrin Outside-In Signaling Activate NADPH-Oxidase 2 to Promote Platelet Activation.
Xu Z, Liang Y, Delaney MK, Zhang Y, Kim K, Li J, Bai Y, Cho J, Ushio-Fukai M, Cheng N, Du X. Xu Z, et al. Arterioscler Thromb Vasc Biol. 2021 May 5;41(5):1638-1653. doi: 10.1161/ATVBAHA.120.315773. Epub 2021 Mar 11. Arterioscler Thromb Vasc Biol. 2021. PMID: 33691478 Free PMC article. - Local Radiotherapy Affects Drug Pharmacokinetics-Exploration of a Neglected but Significant Uncertainty of Cancer Therapy.
Chen YJ, Tsai TH, Wang LY, Hsieh CH. Chen YJ, et al. Technol Cancer Res Treat. 2017 Dec;16(6):705-716. doi: 10.1177/1533034617737011. Epub 2017 Oct 31. Technol Cancer Res Treat. 2017. PMID: 29332468 Free PMC article. Review. - Neutrophils to the ROScue: Mechanisms of NADPH Oxidase Activation and Bacterial Resistance.
Nguyen GT, Green ER, Mecsas J. Nguyen GT, et al. Front Cell Infect Microbiol. 2017 Aug 25;7:373. doi: 10.3389/fcimb.2017.00373. eCollection 2017. Front Cell Infect Microbiol. 2017. PMID: 28890882 Free PMC article. Review. - Molecular control of PtdIns(3,4,5)P3 signaling in neutrophils.
Luo HR, Mondal S. Luo HR, et al. EMBO Rep. 2015 Feb;16(2):149-63. doi: 10.15252/embr.201439466. Epub 2015 Jan 9. EMBO Rep. 2015. PMID: 25576302 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources